Chronic cerebral hypoperfusion (CCH) is a risk factor for the development of vascular dementia (VaD). CCH
participates in a negative role in cognitive impairments. Transient receptor potential vanilloid subtype 1 (TRPV1)
participates in cognition, ischemic damage and neuroprotection. Selective norepinephrine transporter (NET) inhibitors
have a role in cognitive dysfunction and oxidative stress. The role of TRPV1 and NET in CCH induced VaD is still
unknown. The present study has been structured to investigate the role of vanillin; a selective agonist of TRPV1 as well as
atomoxetine; a selective NET inhibitor in CCH induced VaD in mice. Permanent bilateral common carotid arteries
ligation or two vessel occlusion (2VO) technique was used to induce a stage of chronic cerebral hypoperfusion in mice.
2VO animals have shown significant impairment of locomotion (Actophotometer), motor coordination (Rota rod),
learning and memory (Morris water maze). 2VO animals have shown significant reduction in brain catalase, glutathione,
and superoxide dismutase, with significant increase in brain infarct size (TTC staining), malondialdehyde and acetyl
cholinesterase-AChE activity. Whereas, administration of vanillin as well as atomoxetine has significantly attenuated
2VO induced impaired locomotion, motor coordination, learning and memory, brain damage, brain oxidative stress and
higher AChE activity. It may be concluded that 2VO induced CCH has elicited VaD, which was attenuated by vanillin
and atomoxetine. Thus, modulators of vanilloid receptors and norepinephrine transporter may be explored further for their
benefits in CCH induced VaD.